Lexicon Pharmaceuticals has announced the initiation of patient randomization in its Phase 3 SONATA-HCM clinical trial, designed to evaluate sotagliflozin as a potential treatment for adults with symptomatic hypertrophic cardiomyopathy (HCM). The study aims to enroll adults aged 18 years or older diagnosed with either obstructive (oHCM) or non-obstructive (nHCM).
The SONATA-HCM trial is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Lexicon plans to conduct the trial at 130 sites across 20 countries. The primary objective is to assess the efficacy and safety of sotagliflozin in improving symptoms, function, and patient-reported outcomes in individuals with HCM.
Rationale for Sotagliflozin in HCM
Hypertrophic cardiomyopathy affects an estimated 1.1 million people in the United States. Common symptoms include shortness of breath, lightheadedness, fatigue, palpitations, and limitations in physical activity. Despite recent advances, significant unmet needs remain for new therapeutic options.
"SONATA-HCM will evaluate the efficacy of sotagliflozin, a dual SGLT2 and SGLT1 inhibitor, on symptoms, function, and other patient-reported outcomes, as well as safety in patients with symptomatic HCM," said Carolyn Y. Ho, M.D., Cardiology, Brigham and Women’s Hospital, and a co-author of the study abstract.
Sharlene M. Day, M.D., Director, Translational Research, Division of Cardiovascular Medicine and Cardiovascular Institute, University of Pennsylvania Medicine, another co-author, added, "Although HCM is a unique condition, there are overlapping features with other conditions that lead to heart failure, so I’m optimistic that sotagliflozin could work in this patient population."
Sotagliflozin: A Dual SGLT Inhibitor
Sotagliflozin is an oral inhibitor of sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney, while SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in approximately 20,000 patients across multiple clinical studies encompassing heart failure, diabetes, and chronic kidney disease.
Regulatory Strategy
Lexicon intends to submit a supplemental new drug application (sNDA) to the FDA with a broad proposed label to improve symptoms and physical limitations in adults with HCM, contingent upon positive results from the SONATA-HCM trial and interactions with the FDA, according to Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. The company believes sotagliflozin has the potential to become a safe and effective treatment for HCM, either as a standalone therapy or in conjunction with currently available medications.
